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A natural component of human blood has been found to block the HIV virus from infecting cells. And fortunately, tweaking just a few of the amino acids that form the molecule somehow makes its effects 100 times more potent.

Because it works in a different way to existing therapies, the peptide could lead to a novel class of drugs to fight AIDS. There is also evidence that HIV doesn't easily develop resistance to the new compound, which is a major problem with many current HIV treatments.

The molecule, known as VIRIP (virus-inhibitory peptide), binds to a spiky protein on the surface of the HIV virus called gp41. HIV normally uses this protein to make the first contact with and latch onto a human cell, after which it would infect it. But the intervention of VIRIP stops that contact from happening.

...Once they had isolated the protein, the team set about adjusting it to explore which changes to its structure might alter its function, by fiddling with the amino acids in its 20-amino-acid chain. In one instance, they found that adding just one specific amino-acid building block rendered the protein useless in protecting against HIV. "We were surprised it was so specific," says Kirchhoff. "It is really striking." ...VIRIP picks on a fairly stable surface protein, which does not change so much — it works in conjunction with another protein, called gp120, which was recently discovered to be conserved over time. This means that a drug using it should remain effective. "The really good thing is that it targets a very conserved area," says Ray. "It does seem to be a promising candidate."

Please forgive me, I'm new at all this, but don't this information correlate with Dr. Candace Pert's work? By the way, has anybody heard from her lately? I was under the impression, that she was to make a major announcement, sometime at the end of march? While on the subject of apparitions, anybody know anything on Dr. Kangs vaccines?

I am under the impression that a few major announcements are in the pipe. Not just from these camps, but from several. We could see day, not too far from now, where the next generation of therapies are excessive. This is a good thing, of course. We are on the brink of major news in the long term treatment of HIV. Ihave no specifics on this, but having read ever study and report out there over the past 4 years, I can tell you some things are on the very near horizon. It's just a matter of who announces what first. No, not a cure, but a viable, long term, resistent proof therapies are in the works. Just my opinion.

I am under the impression that a few major announcements are in the pipe. Not just from these camps, but from several. We could see day, not too far from now, where the next generation of therapies are excessive. This is a good thing, of course. We are on the brink of major news in the long term treatment of HIV. Ihave no specifics on this, but having read ever study and report out there over the past 4 years, I can tell you some things are on the very near horizon. It's just a matter of who announces what first. No, not a cure, but a viable, long term, resistent proof therapies are in the works. Just my opinion.

Have a great day!

While we're at it, let's also hope for non-toxic, very easy to administer/adhere to, and relatively inexpensive. Fingers crossed.

yes, very cool indeed. I've been holdingout on meds, with the hope that something better was on the horizon, but unfortuneatly I had to start on meds last week, after 20 some years, doctors orders. Where's gene therapy or vaccines when you need them. Hopefully, my expierence with meds will be short lived. Had I listened to docs 6 to 8 years ago, I'd have been knee deep in drug therapy, with major resistance. hope what you've said is true, I could sure use some positive reassureance. once again thanks for the positive news

Discovery of an HIV inhibitor in human blood points to new drug classThus, they showed, VIRIP plays an essential role in the ability of HIV to fuse with and infect its host's immune cells. That unique underlying mechanism ...www.eurekalert.org/pub_releases/2007-04/cp-doa041607.php - Apr 19, 2007 - Similar pages

also here they say...The research done by Münch is based on two factors. It has been known for a long time that endogenous retroviruses constitute an integral part of the human genome (approx. 8%).

i have been writing about this fact on this forum for two months... basically what this mean is...

inside every human dna 8% is acutally retroviruses that got stuck in thier when we were evolving from chimps, shrimps, bats and rats, and those viruses are stuck in our dna all of our... and this got the scientists thinking

if there are so many endogenous retroviruses-- dna of retro viruses stuck in our cells there must be some peptides that have also evolved to supppress these fragments ... and maybe if one is in the blood that will supress achient retrovirus dna that is stuck in our dna maybe there is one peptide molecule that represses hiv naturally that is in the blood already that may be... we can find... and make more of and turn into a medicine... they just found one that suprreesses hiv

so so cool

check my posts from last month i wrote that 8% human dna 8% is acutally retroviruses stuck in there...

now, science is just finding some weird new diseases that pop up in humans when these old 8% human dna 8% is acutally retroviruses -- when they pop out of the dna and start to multiply and suddenily someone has a disease... like... i cant remember which but like ms, md, lypho, cancers etc...

caused by a 100 million year old retrovirus fragment in the bodies own dna that got their many eons ago

The VIRIP peptide is an α1 antitrypsin fragment consisting of 20 amino acids that was isolated from a blood peptide library. Jan Münch is confident about the likelyhood of success as the molecule has proved to be capable of inhibiting all HIV-1 variants tested so far, including patient isolates and HI viruses that have already become resistant to other drugs.

cool this α1 antitrypsin fragment seems to be involved in the diaherrah hiv guys are getting... perhaps the body produces more α1 antitrypsin fragments and is trying to help fight off hiv and that is why they find an elevated level...

Faecal alpha 1 antitrypsin as a marker of gastrointestinal disease in HIV antibody positive individualsD Sharpstone, A Rowbottom, M Nelson and B Gazzard Department of HIV/GUM, Chelsea and Westminster Hospital, London. Hypoalbuminaemia and diarrhoea are common complications of HIV infection and substantial causes of morbidity, but the specific intestinal pathologies that cause enteric protein loss have not been clearly defined. Two hundred and twenty stool samples from patients with a variety of HIV related conditions were analysed for faecal alpha 1 antitrypsin. Patients with intestinal Kaposi's sarcoma had a significantly raised faecal alpha 1 antitrypsin value and hypoalbuminaemia. A faecal alpha 1 antitrypsin value of greater than 0.3 mg/g wet stool has a sensitivity of 94% and a specificity of 76% for the diagnosis of intestinal Kaposi's sarcoma in HIV positive individuals. Patients with cytomegalovirus and bacterial enteritis had raised faecal alpha 1 antitrypsin values but levels were normal for all other intestinal pathologies compared with pathogen negative stool. The combination of faecal alpha 1 antitrypsin concentration greater than 0.2 mg/g, a negative stool culture for enteric bacteria, and the absence of palatal Kaposi's sarcoma has a sensitivity of 55% and specificity of 88% for the diagnosis of enteric cytomegalovirus infection.

The protein metabolic response to HIV infection in young children 1 2 3 - group of 6 »F Jahoor, S Abramson, WC Heird - 2003 - Am Soc Nutrition ... pools of fibrinogen and 1 -antitrypsin in the HIV-infected group were associated with ASRs that were significantly faster than those of the uninfected group.

The protein metabolic response to HIV infection in young children 1 2 3 - group of 6 »F Jahoor, S Abramson, WC Heird - 2003 - Am Soc Nutrition... protein balance because of an inability to down-regulate protein catabolism. ... largerplasma pools of fibrinogen and 1 -antitrypsin in the HIV-infected group

Serpin A1 (alpha1-antitrypsin, alpha1-proteinase inhibitor) has been shown to be a non-cytolytic antiviral factor present in blood and effective against HIV infection. The best known physiological role of serpin A1 is to inhibit neutrophil elastase, a proteinase which is secreted by neutrophils at sites of infection and inflammation. Decreased HIV-infectivity is associated with decreased density of membrane-associated elastase. The enzyme may facilitate binding of the HIV membrane protein gp120 to host cells, and it specifically cleaves SDF-1, the physiological ligand of the HIV-1 co-receptor CXCR4. It has been suggested that one of the actions of serpin A1 as antiviral agent is to reduce HIV infectivity, and this property could be due to elastase inhibition. However, the most dramatic effect of serpin A1 is inhibition of HIV production. In vitro experiments indicate that the C-terminal peptide of serpin A1, produced during the formation of the complex of serpin with serine proteinases, may be responsible for the inhibition of HIV-1 expression in infected cells. This peptide, an integral part of the serpin-enzyme complex, is internalized by several scavenger receptors. Peptides corresponding to the C-terminal section of serpin A1 inhibit HIV-1 long-terminal-repeat-driven transcription and interact with nuclear proteins, such as alpha1-fetoprotein transcription factor. LDL-receptor-related protein 1 (LRP1/CD91), the best known receptor for serpin-enzyme complexes, is up-regulated in monocytes of HIV-1-infected true non-progressors. CD91 could be one of the major players in host resistance against HIV-1. It has the capacity of internalizing antiviral peptides such as serpin C-terminal fragments and alpha-defensins, and is at the same time the receptor for heat-shock proteins in antigen-presenting cells, in which chaperoned viral peptides could lead to the induction of cytotoxic T-cell responses.

I definitely think that these highly conserved parts of HIV - the gp120 b12 region and this new glycoprotein are the way to go. Because the interactions between them and the human CD4 cell are so specific, the virus cannot mutate away from them without being unable to bind to CD4 receptors and infect host cells.

So hopefully we will have drugs with little or no side effects, effective inhibition of HIV, and no potential for mutation. I actually didn't think this was possible until recently - I figured anything with action against HIV could be mutated against, but maybe not.

They can "tweak" VIRIP and make it 100x more effective in the test tube. And it is as effective as T20 at a fraction of the concentration, and is non-toxic up to much higher concentrations. Let's hope that in a few years this is around in the form of a drug we can take.

Hate to be pessimistic but I think "in a few years" will be a bit longer. What is the average time track for drug development from the stage presented in the original article? Much longer as I recall.

Yup, you're right. I was caffeinated when I wrote that!

I think it might actually not take so long as a regular drug. After all, you're dealing with a compound that is already in the body. They've already done some of the animal tests required and some studies in extracted human lymph tissue.

Does anyone have an idea if this type of inhibitor would be able to control/prevent infection in the brain or other hard-to-reach areas? I often wonder about this in many of the new treatments being developed, since the focus is usually on cd4 infection.

Does anyone have an idea if this type of inhibitor would be able to control/prevent infection in the brain or other hard-to-reach areas? I often wonder about this in many of the new treatments being developed, since the focus is usually on cd4 infection.

I would guess that it does. I think a peptide of only 20 amino acids, like VIRIP, should cross the blood-brain barrier without much difficulty.

There are also quite a few drugs in current use that effectively suppress HIV in the brain: AZT, d4T, abacavir and sustiva all cross the blood brain barrier and suppress HIV. Also, immune cells themselves cross the blood brain barrier and combat HIV, so having more healthy CD4s floating around does it's bit.

Substances with a molecular weight higher than 500 daltons (500 u) generally cannot cross the blood-brain barrier, while smaller molecules often can. I think this peptide is much smaller than that so it should pass thru.

This is a major breakthrough in my humble opinion. never have we had a naturally occuring substance that is already in the body that can fight HIV. I hope and pray for all of us and the 15 people a day inside the USA who are still dying everyday from hiv that this gets to market and approved fast.

...the 15 people a day inside the USA who are still dying everyday from hiv...

Really? In the USA? In this day and age? How exactly are these people dying? Do people run out of drug options or something? Now I'm a little confused. I'm new to this virus and reading a statement like that is kind of depressing, especially since everyone I talk to, from doctors to my hiv positive friends tell me that the drugs available now really work well.

I agree with you bizmazek in thinking that this is very important. But I'm not sure that it represents the future of HIV treatment. I think the major problem with it is how do you get a 20-residue peptide into the body? It's not going to be via the GI tract, because it'd be broken down - you're going to have to inject it IV. And unless you come up with a way of formulating it so it persists in the body for a week or more, I wonder if people are going to be able to use it.

This is the reason that soluble CD4 was never used as a therapy - the peptide was just too big to deal with and would have needed IV infusion.

That's an interesting stat. I wonder how far above the baseline of the general population that is. It says 17,011 died with AIDS, not from it - with a million Americans HIV+ and a significant number of them having AIDS diagnoses some of that has got to be non-AIDS related.

8% of every humans dna is retroviruses that got stuck in their during evolution

every human blood has some of this Viral inhibitory protein already in the body most likely

The Viral inhibitory protein they have invented because it is 100x more potent and cannot be mutated around could be a great breakthrough

thousands of liters of blood was filtered to find the discovery

some rare extremely rare diseases are caused when these "8% of every humans dna is retroviruses" fragments breakfree and create disease

the production of nef by hiv infection is the protein that does the majority of the damage to the human body

it is not the infected cd4 cells that die in large numbers because only one in a million are infected, it is the non infected cd4 cells that recieve a homing signal via fas that self distruct because they think their fighting job is over, this was proven at oxford with math models of the immune system

Well, if they can get it down to a fuzeon size molecule I'm a pro with that injection now. I will benefit greatly!

Personally I think injectable are great... when it circumvents the GI system there are no diarrhea side effects. Would you rather prick yourself daily or sit on the toilet for hours on end?

I'd rather get pricked daily

Fuzeon is injected subcutaneously right? I think this thing would have to be injected IV, so I'm not sure you'd be able to do it yourself. But it would be cool if they could tinker with it and you could go to a clinic for 30 mins once weekly...

I believe that this molecule would be small enough to put in a pill and will pass the blood brain barrier.

I think it will probably go through the BBB when it's in the body, yes.

The question is how to get it into the body. I'm not sure putting it in a pill is going to work - it'll get digested and broken down into smaller peptides. I don't think a 20-AA peptide can cross from gut to bloodstream.

This is indeed wonderful and hopeful work and I agree with Matt that targeting these highly conserved parts of HIV is the way to beat out resistance and this looks to be a fantastic target.

Being in the business of developing protein based therapeutics I have a couple comments regarding discussions of pill development and modes of delivery. I do not want to seem pessimistic or negative about this because I think it is a feasible target and could be a very effective therapy.

Having said that, it is very, very difficult to put proteins, even small peptides, in oral delivery forms due to exactly what has been already stated..they will be chopped up in the gut and cannot diffuse out like small molecules (chemicals).

All the protein/peptide based therapeutics (large molecules) we have developed (at my company and in the greater biotechnology industry) are delivered either via IV or subcutaneously (with IV being the predominant route). Additionally, most of the peptides are conjugated to some larger molecule/protein to ensure longer half life and stability in the body after delivery.

One additional comment aside from the delivery discussion is regarding the use of endogenous molecules as therapies. The use of recombinant or synthesized forms of molecules that naturally exist in the body is widespread and has been mostly safe and effective (insulin, factor VIII, erythropoietin) but it could be tricky since reintroduction of these similar molecules into the body could (not will or always) induce an immune response, which could (not will or always) result in an autoimmune state where an immune response directed at the therapy also acts of the native species. This could result in a poor clinical effect and it could have little effect but all in all it is not looked favorably during review for approval by agencies like EMEA and FDA. The reason I point this out is that careful safety and efficacy studies are required even for therapies based on naturally existing molecules (specifically peptides, peptide mimetics and proteins) and the timeline is often longer than for smaller molecule based therapies.

I think this is a worthy pursuit and look forward to reading about more studies. I wanted to put in my two cents from the drug development point of view as part of this discussion. I am almost positive I have rambled and if what I said doesn't make sense let me know. I'm tired but enjoy these types of discussions.